The overall aim of this proposed work is to investigate the possible physiological functions of endorphin, the endogenous ligand for the narcotic receptor. A number of behavioral, pharmacological and anatomical techniques will be employed to study the possible role of endorphin as an analgetic agent, the manner in which it might underlie the development of narcotic tolerance and dependence, and its alteration by environmental stimuli, such as those which induce stress. The narcotic binding procedure will be employed as the measure of endorphin levels in various brain regions, or of its release into the cerebrospinal fluid. In addition, a number of neurochemical and neuroanatomical techniques will be used to investigate the possible interactions of endorphic with other endogenous neuromodulators, particularly the monoamones.